The overall objective of this research project is to clarify at the cell and membrane level the sequential changes in neural, humoral and ionic control mechanisms of vascular smooth muscle (VSM) tone particularly on the venous side of the circulation that are responsible for development of spontaneous hypertension in the animal model and essential hypertension in man. Changes in the electrical and mechanical properties of VSM that control its tone will be measured as a function of age both in vivo and in vitro using the small capacitance and, where possible, resistance vessels of the suffused intestinal mesenteric bed in the spontaneously hypertensive rat (SHR), in its normotensive Wistar-Kyoto control (WKY) and in Wistar (W) rats. In vivo and in vitro measurements will include VSM membrane potentials, vessel diameters, intralumenal pressures and calculated and directly measured wall tension. These measurements will be performed during the following alterations of specific components of control of blood vessel electrical and mechanical properties: (1) Peripheral neural-via suffusion with TTX and 6-hydroxydopamine; (2) central-via phentolamine, propranolol and the neurotransmitter uptake blockers, desmethylmipramine and deoxycorticosterone; (4) direct vascular-via suffusion with altered K ion, Ca2 ion, Ba2 ion, La3 ion, verapamil, norepinephrine with and without TTX; (5) electrogenic pump blockade-via ouabain and altered K ion in the suffusate. Other VSM control components that will be measured in vivo as a function of age include: small mesenteric blood vessel concentrations and turnover rates of catecholamines, and splanchnic sympathetic efferent input. Evaluation of the sequential changes in these variables should help clarify our understanding of the relative importance of aberration in the neurogenic control of VSM tone and its contribution to the genesis of essential hypertension.